Devices and methods for endoscopic patch delivery

ABSTRACT

Systems and methods of delivering a patch to a target site of a patient are described herein. The patch may comprise a biomaterial such as chitosan or extracellular matrix and may be biocompatible and/or bioresorbable. The system may include an endoscope, a patch, and one of an instrument or a cap, the patch being coupled to the respective instrument or cap and detachable therefrom. Methods of delivering the patch to the target site may include introducing an endoscope into a gastrointestinal tract of a patient, e.g., the patch being in a folded or crimped configuration, navigating a distal end of the endoscope proximate a target site; and applying the patch to the target site while releasing the patch from the endoscope.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority from U.S. ProvisionalApplication No. 62/712,361, filed on Jul. 31, 2018, which isincorporated by reference herein in its entirety.

TECHNICAL FIELD

The present disclosure relates generally to medical devices and relatedmethods of preparation and use thereof. More specifically, the presentdisclosure includes devices useful in endoscopic medical procedures,such as applying a patch to tissue for wound treatment.

BACKGROUND

Various medical procedures are used for treatment of tissue. Forexample, an endoscopic procedure may be performed to take tissue samplesfrom the gastrointestinal tract or other organ systems for pathologicalevaluation and/or therapeutic purposes, such as detection and removal ofpre-cancerous mucosal tissue or tumors. Endoscopic mucosal resection(EMR) and endoscopic submucosal dissection (ESD) may be used to separateupper tissue layers to assist in the removal of lesions. A consequenceof such medical procedures can be a wound in need of repair and/orprotection to allow for tissue repair. Other internal wounds or defectssuch as, e.g., inflammation, ulcerations, and the like, can resultnaturally and likewise benefit from therapeutic treatment. Medicaldevices in the form of bandages and dressings can be prepared from avariety of materials. Applying such dressings to internal tissue, e.g.,in an endoscopic procedure, presents particular challenges.

SUMMARY OF THE DISCLOSURE

The present disclosure includes medical systems comprising abiocompatible patch and methods of use thereof, e.g., methods ofdelivering a patch to a target site of a patient. For example, thepresent disclosure includes a medical system that includes an endoscopedefining at least one working channel and a patch comprising abiocompatible material. In some examples herein, the system furthercomprises (a) an instrument comprising a shaft slidably disposed in theworking channel, the patch being coupled to, and releasable from, adistal end of the instrument; or (b) a cap coupled to a distal end ofthe endoscope, the patch covering a distal end of the cap and beingreleasable from the cap. In some examples, the patch comprises abiomaterial such as chitosan, e.g., chitosan acetate and/or chitosanlactate, extracellular matrix, or a combination thereof. Additionally oralternatively, the patch may have a thickness less than 3 mm, such asless than 2 mm or less than 1 mm. According to some aspects of thepresent disclosure, a least a portion of the patch comprises anadhesive, optionally a biocompatible and/or bioresorbable adhesive. Insome examples, the patch is disposed inside the at least one workingchannel of the endoscope in a folded or crimped configuration. In otherexamples, the patch is coupled to an outer surface of the system, suchas the outer surface of a cap coupled to the distal end of theendoscope.

In some examples wherein the system comprises the instrument, the distalend of the instrument is rotatable relative to the shaft of theinstrument. Alternatively, the distal end of the instrument may be fixedto the shaft, such that rotation of the shaft causes a correspondingrotation of the distal end of the instrument. The distal end may have acylindrical shape, for example and/or the distal end may include aballoon. In some examples, the distal end of the instrument includes arim that inhibits or prevents proximal movement of the patch relative tothe instrument. For example, the distal end of the instrument mayinclude a cylinder and optionally a rim at or proximate the proximal endof the cylinder, e.g., to inhibit or prevent proximal movement of thepatch relative to the cylinder and/or relative to the shaft of theinstrument. In some examples, the distal end of the instrument includesa balloon, and the shaft of the instrument comprises an fluid channel incommunication with the balloon. The fluid channel may be coupled to asource of fluid such as, e.g., water, air, or other inert gas.

In some examples wherein the system comprises the cap, the patch may besecured to an outer surface of the cap with a band, e.g., a flexibleband, such as, e.g., an elastic band. According to some aspects of thepresent disclosure, the cap includes a ridge on an outer surface of thecap. Additionally or alternatively, the cap may have a frustoconicalshape. In some examples, the distal end of the endoscope includes anoptical device, and the patch includes an opening aligned with theoptical device. Additionally or alternatively, at least a portion of thepatch covering the optical device may be translucent. In some examples,the entire patch is translucent.

The endoscope of the system may comprise a single working channel or aplurality of channels. In some examples, the system comprises anauxiliary instrument insertable in one or more of the working channels,e.g., to assist in applying the patch to tissue. Such auxiliaryinstruments may include, for example, a forceps or other instrument toassist in manipulating the patch relative to the target site. In someexamples, the endoscope includes a suction channel in communication witha source of suction and/or a fluid channel in communication with asource of fluid such as air or water.

Also disclosed herein is a method of delivering a patch to a target siteof a patient, the method comprising introducing an endoscope into agastrointestinal tract of a patient, wherein the endoscope includes apatch in a folded or crimped configuration, the patch comprising abiocompatible material; positioning a distal end of the endoscopeproximate a target site; and applying the patch to the target site whilereleasing the patch from the endoscope. The target site may includewounded or diseased tissue, for example, or the target site maycorrespond to the site of a prior medical procedure. In some examples,the target site includes a laceration in tissue following endoscopicmucosal resection (EMR), endoscopic submucosal dissection (ESD), ortissue biopsy. In some examples, wherein the target site includes ananastomosis, e.g., such that the patch inhibits or prevents leakage. Asmentioned above, the patch may comprise a biomaterial such as chitosan,e.g., chitosan acetate and/or chitosan lactate, extracellular matrix, ora combination thereof; and/or the patch may comprise an adhesive, suchas, e.g., a biocompatible and/or bioresorbable adhesive.

According to some aspects of the present disclosure, the method furthercomprises introducing an instrument comprising a shaft into a workingchannel of the endoscope, the patch being disposed on a distal end ofthe instrument. For example, applying the patch to the target site mayinclude unrolling the patch from the distal end of the instrument.Further, for example, the distal end of the instrument may include acylinder, the patch being disposed on a surface of the cylinder, whereinapplying the patch to the target site includes rotating the cylinder,e.g., relative to the target site and/or relative to the shaft of theinstrument. In at least one example, the cylinder includes a rim thatprevents proximal movement of the patch relative to the shaft.

In some examples, the distal end of the instrument includes a balloon,and the shaft of the instrument comprises a fluid channel incommunication with the balloon, e.g., for inflation and deflation of theballoon. For example, the patch may be disposed on a surface of theballoon in a folded configuration, the method comprising expanding theballoon to unfold the patch, e.g., to apply the patch to the targetsite.

As mentioned above, in some examples herein, the endoscope includes acap coupled to a distal end of the endoscope, the patch covering adistal end of the cap and being releasable from the cap. Thus, forexample, applying the patch to the target site may include releasing thepatch from the cap, optionally by applying pressure to the patch with afluid (e.g., air or water) and/or with an instrument via a workingchannel of the endoscope.

Also provided herein is a method of delivering a patch to a target siteof a patient, the method comprising introducing a system comprising anendoscope into a gastrointestinal tract of a patient, wherein the systemincludes a patch comprising a biocompatible material and one of (a) aninstrument comprising a shaft slidably disposed in a working channel ofthe endoscope, the patch being coupled to, and releasable from, a distalend of the instrument; or (b) a cap coupled to a distal end of theendoscope, the patch covering a distal opening of the cap and beingreleasable from the cap. The method may further comprise positioning adistal end of the endoscope proximate a target site; and applying thepatch to the target site while releasing the patch from the system. Insome examples, the patch is coupled to the distal end of the instrumentor the cap in a folded or crimped configuration. According to someaspects, releasing the patch includes blowing air or spraying water froma channel of the endoscope onto the patch. In some examples herein, thedistal end of the instrument includes a cylinder that comprises a rim,the patch being disposed on a surface of the cylinder distal to the rim.

BRIEF DESCRIPTION OF THE FIGURES

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various exemplary embodiments andtogether with the description, serve to explain the principles of thedisclosed embodiments.

FIG. 1 shows an exemplary endoscope, in accordance with some aspects ofthe present disclosure.

FIGS. 2A-2C illustrate delivery of a patch with an exemplary system, inaccordance with some aspects of the present disclosure.

FIGS. 3A-3D illustrate delivery of a patch with an exemplary system, inaccordance with some aspects of the present disclosure.

FIG. 4A shows an exemplary endoscope cap, and FIGS. 4B and 4C illustratedelivery of a patch using the endoscope cap, in accordance with someaspects of the present disclosure.

FIGS. 5A-5D illustrate delivery of a patch with an exemplary system, inaccordance with some aspects of the present disclosure.

FIGS. 6A-6C illustrate delivery of a patch with an exemplary system, inaccordance with some aspects of the present disclosure.

FIG. 7 shows an exemplary system, in accordance with some aspects of thepresent disclosure.

DETAILED DESCRIPTION

Particular aspects of the present disclosure are described in greaterdetail below. The terms and definitions provided herein control, if inconflict with terms and/or definitions incorporated by reference.

As used herein, the terms “comprises,” “comprising,” or any othervariation thereof are intended to cover a non-exclusive inclusion, suchthat a process, method, composition, article, or apparatus thatcomprises a list of elements does not include only those elements, butmay include other elements not expressly listed or inherent to suchprocess, method, composition, article, or apparatus. The term“exemplary” is used in the sense of “example” rather than “ideal.”

As used herein, the singular forms “a,” “an,” and “the” include pluralreference unless the context dictates otherwise. The terms“approximately” and “about” refer to being nearly the same as areferenced number or value. As used herein, the terms “approximately”and “about” should be understood to encompass ±5% of a specified amountor value.

Embodiments of the present disclosure include medical systems andmethods for endoscopic delivery of patches for treating tissue. Thepatches herein may comprise one or more biomaterials (e.g., materialsthat are biocompatible and/or derived from biological materials), whichmay be at least partially or completely bioresorbable. For example, uponapplication to tissue, at least a portion of the patch may dissolveand/or be absorbed by the body over time. In some cases, a portion ofthe patch may be shed from the site of application to be absorbed orremoved by the gastrointestinal system.

The patches herein may serve as a protective layer, a barrier againstleaks, a barrier against perforations, a defect closure, a scaffold topromote cell growth, and/or as a hemostatic agent, among other uses.Further, for example, the patches herein may be used to treat varioustypes of tissues, including wounded or diseased tissue, such as burns,lacerations, lesions, inflammation, ulceration, perforations,microperforations, and other sites in need of treatment or repair. Thepatches herein may be used as an alternative to, or in combination with,sutures, staples, adhesive, and other methods for securing or protectingtissue. In at least one example, the patch may be applied to serve as ahemostatic agent, e.g., to prevent or inhibit bleeding of tissue at atarget site.

Exemplary sites to which the patches herein may be applied include, butare not limited to, tissues of the gastrointestinal system such as,e.g., the esophagus, the stomach, the small intestine (e.g., duodenum,jejunum, or ileum), and/or the large intestine (e.g., cecum, colon,rectum, or anal canal). In some examples, an anastomotic resection ofthe small or large intestine may lead to a risk of leaks between suturelines. The patches herein may be applied to such junctions to serve as abarrier against leakage. In some examples, the patches herein may beapplied to a fistula, e.g., an intestinal fistula, to serve as a barrieragainst leakage of fluid and/or to cover a sac to prevent it from boringinto surrounding anatomy Further, for example, the patches herein may beuseful for patients that have inflammatory bowel disease (IBD), e.g.,applying the patch to a subsidiary disease fistula associated with IBD,wherein the fistula connects intestinal lumens.

In some examples herein, the patch is delivered endoscopically,optionally in conjunction with a medical procedure such as endoscopicmucosal resection (EMR), endoscopic submucosal dissection (ESD), ortissue biopsy. For example, a patch may be delivered endoscopically to atarget site to assist the body in regrowing tissue layers removed viaESD or due to ulceration of the mucosal layer. Exemplary biomaterialssuitable for the patches herein include, but are not limited to,chitosan, extracellular matrix (ECM), and other biomaterials comprisingstructural polysaccharides, and combinations thereof.

In some examples herein, the patch comprises chitosan. Chitosan is alinear polysaccharide formed of glucosamine units derived from chitin,the structural component of crustacean exoskeletons.

Chitosan is typically prepared by deacetylation of chitin with analkaline reagent such as sodium hydroxide, yielding a water-solublematerial. Chitosan is antimicrobial and has natural bioadhesiveproperties that allows it to bind to negatively charged surfaces such asmucosal membranes.

The patches herein may comprise chitosan in the form of a salt. Forexample, salts may be prepared by combining chitosan with a suitableconjugate acid such as acetic acid (forming chitosan acetate) or lacticacid (forming chitosan lactate). Other possible organic acids include,but are not limited to, succinic acid (chitosan succinate), glutamicacid (chitosan glutamate), glycolic acid (chitosan glycolate), andcitric acid (chitosan citrate). In an exemplary procedure to prepare achitosan salt, chitosan is suspended in water at room temperature,followed by the addition of an organic acid (e.g., acetic acid and/orcitric acid) to form a gel. The gel is then dried into a film or sheetof desired thickness and dimensions. Without intending to be bound bytheory, it is believed that the acid provides for a cross-linkedstructure that provides sufficient integrity and strength for use as aprotective layer when applied to tissue.

In some examples herein, the patch comprises extracellular matrix (ECM).ECM is a complex and naturally-occurring structural material foundwithin tissues that surround and support cells within tissues and organsof living creatures. It makes up the area external to cells and providesphysical scaffolding as well as biochemical and biomechanical cues thatdirect cell function. ECM has been described as the glue that holdscells within a tissue together. ECM typically comprises structuralproteins and polysaccharides, as well as various growth factors. ECMmaterials can provide a generally dynamic structure that adapts to fitthe surrounding environment.

The chemical composition of ECM can vary depending on its source, e.g.,the type of tissue from which it is derived. For example, ECM may bederived from various types of collagenous tissue. ECM suitable for thepresent disclosure may be derived from any suitable types of tissue,including, but not limited to, tissues of the spleen, kidney, liver,lung, pancreas, gall bladder, or stomach. Further, the tissue may beobtained from various types of native tissues including, but not limitedto, porcine, bovine, ovine, and human tissue.

The patches herein may be formed into any suitable shape and dimensions,e.g., based on the nature of the target tissue site. In some examples,the thickness of the patch may be on the order of millimeters, e.g.,ranging from about 0.1 mm to about 5.0 mm, from about 0.2 mm to about3.0 mm, from about 0.5 mm to about 2.0 mm, or from about 0.8 mm to about1.0 mm, e.g., a thickness of about 0.4 mm, about 0.5 mm, about 0.6 mm,about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1.0 mm, about 1.1 mm,about 1.2 mm, about 1.3 mm, about 1.4 mm, or about 1.5 mm. In at leastone example, the thickness of the patch is less than 3 mm, less than 2mm, less than 1 mm, or less than 0.5 mm. According to some aspects ofthe present disclosure, the thickness may be uniform. The patches hereinmay be at least partially translucent in some cases, e.g., allowinglight to pass therethrough. The patch may have any shape such as, e.g.,square, rectangular, oval, circular, among other possible shapes. Insome examples, the patch has a tubular shape, e.g., a thin-walledcylinder, suitable for application to a body lumen such as the esophagusor small or large intestine.

The patches according to the present disclosure may be pliable andbendable. For example, the patch may be formed into a planar film,sheet, or disc capable of being folded, crimped, or otherwisemanipulated into a temporarily non-planar configuration within aconfined space. Thus, for example, the patch may be folded, curved, orcrimped within a confined enclosure such as a sheath or lumen forsuitable delivery via an endoscope. Once released, the patch may recoverits original planar configuration.

The patch may be substantially dry during delivery to a target site. Insome examples herein, the patch may be moistened during delivery orshortly following release from a delivery instrument. For example, thepatch may be exposed to water via a fluid channel of an endoscope and/orthrough contact with bodily fluids or humidity inside the body. Whenexposed to moisture, the patch may absorb the fluid, causing the patchto swell or expand. For example, the patch, when dry, may besubstantially paper-like, and when wet, may take on a more jelly-likeconsistency. According to some aspects of the present disclosure,moistening the patch may assist in its application to tissue.

In some examples herein, the patch comprises an adhesive, e.g., toassist in applying the patch to tissue and/or maintaining the patch inplace after application, and/or to assist in delivery of the patch tothe target site. Adhesives suitable for the present disclosure may benatural, e.g., comprising a natural polymer or derived from a naturalpolymer, or synthetic. Exemplary adhesives include, but are not limitedto, gelatin (including, e.g., thrombin/gelatin), fibrin (e.g., fibringlue), cyanoacrylate, polyethylene glycol (PEG), and albumin (including,e.g., albumin glutaraldehyde). The adhesive may be at least partiallyresorbable.

The choice of adhesive may be at least partially based on the desiredadhesion strength, bioresorbable properties, and/or the nature of thetarget site to which the patch is being applied. For example, arelatively stronger adhesive may be desired for a patch comprising ECMthan for a patch comprising chitosan, which has natural bioadhesiveproperties. Further, for example, a patch intended for application to arelatively large wound or defect site, may comprise adhesive to furtherassist with securing the patch to the tissue. Patches according to thepresent disclosure may comprise adhesive applied to one area or two ormore areas, e.g., opposing ends. In some examples, the patch does notinclude an adhesive.

Medical systems according to the present disclosure may comprise aninstrument or cap providing a surface for delivery of a patch comprisinga biomaterial or combination of biomaterials as described above and/orelsewhere herein. The systems herein may comprise an endoscope, thepatch or patches to be delivered, and/or one or more auxiliaryinstruments such as, e.g., forceps, an imaging device, or an opticaldevice, etc. The patch or patches may be delivered through the workingchannel of an endoscope, for example, or with the assistance of a capcoupled to the distal end of an endoscope.

FIG. 1 shows an exemplary endoscope 100 useful for some aspects of thepresent disclosure, the endoscope 100 including a controller 102 and ashaft 104 extending distally from the controller 102 to a distal end106. The controller 102 may have any suitable shape and steeringmechanism(s) to allow an operator to navigate the shaft 102 throughtortuous anatomy and/or towards a site of interest. Accordingly, theshaft 104 may be sufficiently flexible to maneuver through differentanatomical structures, including portions of the gastrointestinalsystem.

Any suitable steering mechanism may be used. For example, the steeringmechanism may comprise a plurality of steering wires coupling thecontroller 104 to the shaft 102, e.g., to transmit user input from thecontroller 102 to the shaft 104 to articulate or deflect the shaft 104along one or more planes. As shown in FIG. 1, for example, thecontroller 102 may include one or more actuators, e.g., first and secondactuators 112, 114 to control deflection of the distal end 106 of theshaft 104 in two different planes, e.g., along the xy plane via actuator112 and along the yz plane via actuator 114. Concerted movement of theactuators 112, 114 may achieve deflection in a plurality of otherplanes, e.g., providing for 360 degree manipulation of the shaft 104.Other steering mechanisms suitable for manipulating the shaft 102 may beused, including, but not limited to, other types of mechanicalmechanisms and electrical mechanisms. For example, the controller 102may be in electrical communication with various portions of the shaft104, such that user input at the actuator 112, 114 may be converted toelectrical signals to control deflection of the distal end 106 of theshaft 104.

The shaft 104 may include one or more working channels (e.g., workingchannel 120) in communication with one or more corresponding ports(e.g., port 110) of the controller 102. One or more instruments may beinserted into the working channel 120 via the port 110 for performing amedical procedure. Exemplary instruments include, but are not limitedto, the instruments illustrated in FIGS. 2A-2C, 3A-3D, 5A-5D, and 7(discussed below), and/or other instruments such as forceps, scissors,scalpels, snares, biopsy brushes, optical devices, or imaging devices.In some examples, the controller 102 includes only one port 110 or mayinclude two or more ports each in communication with a separate workingchannel (see, e.g., working channels 720 and 722 in FIG. 7). In someexamples, the controller 102 may include controls for suction and/orfluids such as a suction valve 113 and a fluid valve 115. Thus, forexample, the suction valve 113 may be in communication with a suctionchannel of the shaft 104 and the fluid valve 115 may be in communicationwith a fluid channel of the shaft 104.

FIGS. 2A-2C illustrate an exemplary system comprising a deliveryinstrument 250 and method of delivering a patch to a target site usingthe system, according to some aspects of the present disclosure.Specifically, the instrument 250 is shown disposed within the workingchannel 220 of an endoscope shaft 204 extending to distal end 206. Whileonly one working channel is shown, the method illustrated is equallyapplicable to an endoscope having a plurality of working channels, oneof which houses the instrument 250. Instrument 250 includes a shaft 252and a cylinder 254 at the distal end of the shaft 252, e.g., similar toa drum or a spool. In some examples, the cross-section of the cylinder254 may be greater than the cross-section of the shaft 252.

According to some aspects of the present disclosure, the cylinder 254 isrotatable relative to the shaft 252. For example, the cylinder 254 maybe free-moving and capable of free rotation relative to the shaft 252,similar to a wheel. Alternatively, the instrument 250 may include amechanism to provide for controlled rotation of the cylinder 254, suchas a mechanical lever or electronic switch coupled to the cylinder 254via the shaft and located on a proximal handle of the instrument 250(e.g., the handle being proximal to the port of the endoscope, e.g.,port 110 of FIG. 1). In some examples, the cylinder 254 may be fixedrelative to the shaft 252, such that rotation of the shaft 252 relativeto the working channel 220 causes corresponding rotation of the cylinder254.

The dimensions of the cylinder 254 may be selected to accommodate apatch 800 radially between the outer surface of the cylinder 254 and theinner surface of the working channel 220. That is, the patch 800 may bewrapped or otherwise disposed on the outer surface of the cylinder 254.The proximal end of the cylinder 254 as shown includes a raised surface,e.g., rim 256, to help maintain the position of the patch 800 and toprevent proximal movement of the patch 800 as the instrument 250 slidesalong the working channel 220. The rim 256 is an annular flange havingan outer diameter greater than the outer diameter of the cylinder 254.Additionally or alternatively, the surface of the patch 800 in contactwith the cylinder 254 may include an adhesive to secure the patch 800 tothe instrument 250. The adhesive may be chosen to have a strengthsufficient to prevent movement of the patch 800 relative to theinstrument during delivery while allowing for release of the patch 800upon contact of the patch 800 with tissue.

In some examples, the system may include a catheter or sleeve betweenthe instrument 250 and the working channel 220. For example, thecatheter or sleeve may be disposed radially outside the shaft 252 (andthe cylinder 254 and the patch 800 disposed on the cylinder 254), andthe inner surface of the working channel 220, e.g., to protect the patch800 during delivery. In such cases, the instrument 250 may be preloadedthrough the protective catheter/sleeve to prevent the patch 800 frommoving, the instrument 250 then moved distally relative to thecatheter/sleeve to deploy the patch 800. An adhesive as discussed abovemay additionally be used, or the catheter/sleeve may be sufficient tomaintain the position of the patch 800 prior to deployment, without anadhesive.

During delivery, the instrument 250 is initially entirely disposedwithin the working channel 220 as shown in FIG. 2A. Once the shaft 204is proximate the tissue wall 50 that includes the target site, theinstrument 250 may be moved distally to exit the working channel 220 asshown in FIG. 2B. The shaft 204 and/or the instrument 250 then may bemanipulated to allow the patch 800 to contact the tissue wall 50 at oradjacent to the target site as shown in FIG. 2C. The portion of thepatch 800 in contact with the tissue wall 50 may attach to the tissue(optionally with the assistance of an adhesive) and release from thesurface of the cylinder 254 while the remainder of the patch 800 remainsdisposed on the cylinder 254. The cylinder 254 then may be rotated abouta longitudinal axis of the cylinder 254 relative to the tissue wall 50,to apply the remainder of the patch 800 to the tissue wall 50, includingcovering the target site, while releasing (e.g., unwinding) the patch800 from the cylinder 254.

The patch 800 may be secured to the tissue wall 50 with or without anadhesive. For example, the biomaterial of the patch itself may haveadhesive properties and/or may preferentially adhere to the tissue. Insome examples, an auxiliary instrument such as a forceps may be used toassist in removing the patch 800 from the instrument 250 and/or applyingthe patch 800 to the tissue wall 50. See, e.g., FIG. 7 discussed below.

FIGS. 3A-3D illustrate another exemplary system and method of deliveringa patch according to some examples of the present disclosure.Specifically, an instrument 350 is shown disposed within the workingchannel 320 of an endoscope shaft 304 extending to a distal end 306.Again, only one working channel is shown for illustration purposes,however, the method illustrated is equally applicable to an endoscopehaving a plurality of working channels. Instrument 350 as shown includesa shaft 352 that terminates in a distal end 354.

During delivery, the instrument 350 is initially entirely disposedwithin the working channel 320 as shown in FIG. 3A. A patch 820 formedas a film or sheet may be disposed on the distal end 354 of the shaft352 in a folded, crimped, or collapsed configuration suitable fordelivery. For example, the patch 820 may be sufficiently pliable toallow the patch 820 to be folded in the confined space of the workingchannel 320 but then unfold when released from the working channel 320.As shown in FIG. 3A, the patch 820, much like an umbrella, extendsproximally around the shaft 352 with its edges positioned proximal tothe distal end 354 of the shaft 352 and radially between the outersurface of the shaft 252 and the inner surface of the working channel320.

Once the distal end 306 of the endoscope shaft 304 is proximate thetarget site, e.g., facing the tissue wall 60 that contains the targetsite as shown in FIG. 3B, the instrument 350 may be moved distally toexit the working channel 320. As the patch 820 is released from theworking channel 320, the edges of the patch 820 may unfold as shown inFIGS. 3B and 3C, e.g., the patch 820 being sufficiently flexible toadopt the folded configuration inside the working channel 320 butrecovering its original, unfolded configuration when unconstrained. Forexample, the edges of the patch 820 may unfold or expand when unconfinedfrom the working channel 320 to recover the original, unfoldedconfiguration of the patch 820, as shown in FIG. 3C. Finally, theinstrument 350 may be further advanced distally to apply the patch tothe tissue wall 60, thus covering the target site. In some cases, thepatch 820 may be sufficiently adhered to the distal end 354 of the shaft352, e.g., with an adhesive to allow the patch 820 to remain secured tothe instrument 350 until it comes into contact with the tissue wall 60.Pressure then may be applied to the patch 820 with the shaft 352 tosecure the patch 820 to the tissue wall 60. In some examples, the patch820 may preferentially adhere to the tissue wall 60. In some examples,an auxiliary instrument such as a forceps may be used to assist inremoving the patch 820 from the instrument 350. Further, in someexamples, water and/or positive air pressure may be applied to the patch820 to assist in application to the tissue wall 60. In cases where wateris introduced through the working channel 320 or another channel of theendoscope, e.g., a fluid channel, the patch 820 may absorb the fluid andexpand. Moistening the patch 820 may enhance its ability topreferentially attach to the tissue wall 60.

FIG. 4A shows a cap 430 that may be used in some methods herein. The cap430 defines a lumen and extends from a proximal end 434 to a distal end438 in a generally frustoconical shape. The outer surface of the cap 430includes a raised portion, e.g., ridge 435, which may extendcircumferentially along the cap 430 in a direction perpendicular ortransverse to the length of the cap 430. In some examples, the ridge 435may extend along only a portion of the circumference of the cap 430and/or the ridge 435 may be configured as a plurality of raised surfacesgenerally arranged in a circumferential pattern. According to someaspects of the present disclosure, the cap may be at least partially orcompletely transparent. In other examples, the cap may be at leastpartially or completely opaque.

The proximal end 434 of the cap 430 is configured to fit onto the distalend of an endoscope, e.g., distal end 406 of endoscope shaft 404 inFIGS. 4B and 4C. Any suitable method or features for attaching the cap430 to the endoscope may be used. For example, the cap 430 may be formedof a flexible material, e.g., flexible plastic, such that the proximalend 434 of the cap 430 may surround the distal end of the endoscope in atight, friction fit. Other possible features include, but are notlimited to, tabs or threads. A patch 840 is coupled to the distal end438 of the cap 430, such that the patch 840 extends across, and covers,the distal opening of the lumen of the cap 430. The patch 840 may extendproximally, such that a portion of the patch 840 extends over the ridge435 with the edges 842 of the patch 840 proximal to the ridge 435. Aband 470 is disposed on the proximal side of the ridge 435, over thepatch 840 as shown in FIG. 4B, to secure the patch 840 in place andprevent distal movement of the patch 840 relative to the cap 430. Insome examples, the patch 840 may extend further proximal to the ridge435 than shown in FIG. 4B, e.g., closer to the distal end 406 of theendoscope shaft 404. The band 470 may be elastic and flexible, e.g.,comprising a material such as plastic or silicone. In some examples, theendoscope may include an optical device 425 to assist in viewing thetarget site during delivery. In some examples, the portion of the patch840 that overlays the optical device 425 may be cut to allow a windowthrough which a user may see the tissue wall 60 via the optical device425.

To deliver the patch 840 to the target site of a tissue wall 60, the cap430 may be coupled to the distal end 406 of the endoscope with the patch840 and band 470 attached as described above. Once the distal end 406 isproximate the target site, e.g., facing the tissue wall 60 that containsthe target site as shown in FIG. 4C, the endoscope may be moved distallyto press the patch 840 against the tissue wall 60, such that the patch840 covers all or some of the target site. In order to release the patch840 from the cap 430, the band 470 may be cut so that it uncovers thepatch 840. For example, the band 470 may be attached to a mechanism ofdeployment affixed temporarily, for the purposes of the procedure, tothe working channel, handle, or other portion of the endoscope, suchthat a user may actuate/tighten the wire to cut the band 470, e.g., viaa suitable actuator (e.g., knob, wheel, gear, button, pull-tab, etc.)attached or otherwise coupled to the wire. In some examples, the wiremay be tied to the band and extend distally alongside the endoscopeshaft or through the a working channel 420 of the endoscope, e.g., thewire passing through a hole in the cap 430 or an opening between the cap430 and the distal end 406 of the endoscope. A portion of the band 470may be tethered to the cap 430 and/or the endoscope to avoid loss of theband 470 during delivery of the patch 840.

In some cases, the pressure applied to the patch 840 with the endoscopein combination with release of the band 470 may be sufficient toentirely release the patch 840 from the endoscope and cap 430.Additionally or alternatively, insufflation and/or water pressure may beused to decouple the patch 840 from the cap 430 by blowing air orspraying water from a fluid channel of the endoscope against the side ofthe patch 840 facing the endoscope.

FIGS. 5A-5D illustrate yet another exemplary system and method accordingto some aspects of the present disclosure. Specifically, an instrument550 is shown disposed within the working channel 520 of an endoscopeshaft 504 extending to a distal end 506. Only one working channel isshown for illustration purposes, however, the method illustrated isequally applicable to an endoscope having a plurality of workingchannels. Instrument 550 includes a shaft 552 coupled to an inflatabledevice, e.g., balloon 556. The shaft 552 may include a fluid channel,e.g., coupled to a source of fluid such as air or water, incommunication with the balloon 556 for inflation and deflation.

A patch 860 is disposed on the outer surface of the balloon 556, e.g.,in a folded or crimped state, while the balloon 556 is deflated. Thefolds may allow for the patch 860 to accommodate expansion of theballoon 556. In some examples, the patch 860 may have a tubular shapeand completely surround the balloon 556, as shown. In other examples,the patch 860 may be configured as a film or sheet disposed on only aportion of the circumference of the balloon 556.

During delivery, the endoscope is inserted into a body lumen adjacent toa tissue wall 70 that includes a target site 75, such as a lesion orother wound. The instrument 550 is initially entirely disposed withinthe working channel 520 as shown in FIG. 5A. Once the shaft 504 of theendoscope is proximate the target site 75, the instrument 550 may bemoved distally to exit the working channel 520, as shown in FIG. 5B. Theinstrument 550 is advanced, or the endoscope is retracted or withdrawn,such that the balloon 556 and patch 860 disposed thereon, are outsidethe working channel 520, as shown in FIG. 5C. Finally, the balloon 556is inflated, thus expanding and unfolding the patch 860 such that thepatch 860 contacts the tissue wall 70 and the target site 75, as shownin FIG. 5D. Upon contacting the tissue, the patch 860 may preferentiallyattach to the tissue and release from the balloon 556. In some examples,the patch 860 may be secured to the balloon 556 with an adhesive withsufficient strength to prevent movement of the patch 860 relative to theballoon 556 during delivery while allowing for release of the patch 860upon contact with the tissue wall 70. Once the patch 860 is released,the balloon 556 may be deflated and the instrument 550 and endoscopewithdrawn from the body lumen.

FIGS. 6A-6C illustrate another example of applying a patch 880 to atissue wall 90 of a patient. For example, the tissue wall 90 may be partof the patient's gastrointestinal system, such as the esophagus, thestomach, the small intestine (e.g., duodenum, jejunum, or ileum), or thecolon. The tissue wall 90 includes a target site 95 such as a cut,laceration, or other wound. For example, the target site 95 may resultfrom torn or cut tissue, e.g., due to an injury or as part of a medicalprocedure, such as a biopsy.

The patch 880 may have opposing ends, labeled 880 a and 880 b, that areapplied to areas on either side of the target site 95, and a middleportion 880 c between the two ends. The first end 880 a may be appliedand secured to the tissue wall 90 adjacent to the target site 95, e.g.,via natural adhesive properties of the patch 880 or a suitable adhesiveapplied as discussed above. The patch 880 then may be manipulated toapply the second end 880 b to the tissue wall 90 on the opposite side ofthe target site 95, such that the patch 880 acts to bring the sides ofthe target site 95 together to close the wound. The patch 880 thereforemay have enough structural integrity to withstand manipulation and tosecure the sides of the wound together. In some examples, at least aportion of the patch 880 may stretch to facilitate placement andapplication of the patch 880 to the target site 95. For example, middleportion 880 c may be sufficiently resilient to allow for application ofthe first and second ends 880 a, 880 b on opposing sides of the targetsite 95 and then spring back to its original shape to bring the sides oftarget site 95 together. Each end 880 a, 880 b may include a suitableadhesive to promote and facilitate attachment of the patch 880 to thetissue wall 90. In some examples, the middle portion 880 c of the patch880 does not include adhesive.

The patch 880 may be delivered to the target site 95 via any suitablemethod, including, for example, the methods illustrated in theaccompanying figures. For example, the patch 880 may be delivered usingthe system illustrated in FIG. 7, e.g., via an endoscope 700 that mayinclude any of the features of endoscope 100 of FIG. 1. The endoscopeshaft 704 includes a working channel 720 that accommodates a deliveryinstrument 750 equipped with the patch 880, wherein the instrument 750may include any of the features of instrument 250 of FIGS. 2A-2C. Theendoscope 700 includes a second working channel 722 that accommodates aforceps 790. The patch 880 may be released from the instrument 750 byrotating the distal end 754 of instrument 750 relative to the shaft 752.For example, the first end 880 a may be pressed to a portion of thetissue 90 adjacent to the target site 95 with sufficient pressure sothat it adheres to the tissue 90. Additional rotation may release theremaining portion of the patch 880 from the distal end 754, includingsecond end 880 b. Finally, the forceps 790 may be used to grasp thesecond end 880 b of the patch 880 and apply it to the portion of thetissue 90 adjacent to the opposite side of the target site 95. Theinstrument 750 optionally may be withdrawn into the working channel 720to provide working space for the forceps 790. In some examples, theendoscope 700 may include only one working channel 720, the instrument750 being withdrawn from the working channel 720 before introducing theforceps 790 into the same working channel 720.

Other embodiments of the present disclosure will be apparent to thoseskilled in the art from consideration of the specification and practiceof the embodiments disclosed herein. It is intended that thespecification and examples be considered as exemplary only, with a truescope and spirit of the present disclosure being indicated by thefollowing claims.

We claim:
 1. A method of delivering a patch to a target site of apatient, the method comprising: introducing an endoscope into agastrointestinal tract of a patient, wherein the endoscope includes apatch in a folded or crimped configuration, the patch comprising abiocompatible material; positioning a distal end of the endoscopeproximate a target site; and applying the patch to the target site whilereleasing the patch from the endoscope.
 2. The method of claim 1,wherein the target site includes a laceration in tissue followingendoscopic mucosal resection (EMR), endoscopic submucosal dissection(ESD), or tissue biopsy; or wherein the target site includes ananastomosis.
 3. The method of claim 1, wherein the patch compriseschitosan, extracellular matrix, or a combination thereof.
 4. The methodof claim 1, further comprising introducing an instrument comprising ashaft into a working channel of the endoscope, the patch being disposedon a distal end of the instrument.
 5. The method of claim 4, whereinapplying the patch to the target site includes unrolling the patch fromthe distal end of the instrument.
 6. The method of claim 4, wherein thedistal end of the instrument includes a cylinder, the patch beingdisposed on a surface of the cylinder, and wherein applying the patch tothe target site includes rotating the cylinder.
 7. The method of claim6, wherein the cylinder includes a rim that prevents proximal movementof the patch relative to the shaft.
 8. The method of claim 4, whereinthe distal end of the instrument includes a balloon, and the shaft ofthe instrument comprises a fluid channel in communication with theballoon.
 9. The method of claim 8, wherein the patch is disposed on asurface of the balloon in a folded configuration, the method furthercomprising expanding the balloon to unfold the patch.
 10. The method ofclaim 1, wherein the endoscope includes a cap coupled to a distal end ofthe endoscope, the patch covering a distal end of the cap and beingreleasable from the cap.
 11. The method of claim 10, wherein the patchis secured to an outer surface of the cap with a flexible band.
 12. Themethod of claim 10, wherein the cap has a frustoconical shape and aridge on an outer surface of the cap.
 13. The method of claim 10,wherein a distal end of the endoscope includes an optical device, andthe patch includes an opening aligned with the optical device.
 14. Amethod of delivering a patch to a target site of a patient, the methodcomprising: introducing a system comprising an endoscope into agastrointestinal tract of a patient, wherein the system includes a patchcomprising a biocompatible material and one of: an instrument comprisinga shaft slidably disposed in a working channel of the endoscope, thepatch being coupled to, and releasable from, a distal end of theinstrument; or a cap coupled to a distal end of the endoscope, the patchcovering a distal opening of the cap and being releasable from the cap;positioning a distal end of the endoscope proximate a target site; andapplying the patch to the target site while releasing the patch from thesystem.
 15. The method of claim 14, wherein the patch is coupled to thedistal end of the instrument or the cap in a folded or crimpedconfiguration.
 16. The method of claim 14, wherein releasing the patchincludes blowing air or spraying water from a channel of the endoscopeonto the patch.
 17. The method of claim 14, wherein the distal end ofthe instrument includes a cylinder that comprises a rim, the patch beingdisposed on a surface of the cylinder distal to the rim.
 18. The methodof claim 14, wherein applying the patch to the target site includesunrolling the patch from the distal end of the instrument.
 19. A medicalsystem comprising: an endoscope defining at least one working channel; apatch comprising a biocompatible material; and an instrument comprisinga shaft slidably disposed in the working channel, the patch beingcoupled to, and releasable from, a distal end of the instrument; or acap coupled to a distal end of the endoscope, the patch covering adistal end of the cap and being releasable from the cap.
 20. The medicalsystem of claim 19, wherein the system comprises the instrument, and thedistal end of the instrument includes a cylinder rotatable relative tothe shaft, the cylinder comprising a rim that inhibits or preventsproximal movement of the patch relative to the instrument.